Research efforts in the Neurotoxicology/Neurodegenerative Disease Research Core will be under the direction of Dr. Richard Mayeux and will span clinical, epidemiological, and mechanistic studies of lead and mercury poisoning and neurodegenerative diseases including Parkinson s and Alzheimer?s disease. It is anticipated that Dr. Mayeux will form task-oriented working groups which will focus on specific problems within areas of interest. Members of the faculty, postdoctoral fellows and doctoral students will meet monthly to discuss topics of ongoing interest in one of the following areas: 1) gene-environment interactions in the neurodegenerative diseases of aging; 2) molecular mechanisms involved in the perturbation of iron metabolism as it relates to Parkinsonism; 3) genetic susceptibility to Parkinson s disease in first-degree relatives of both sporadic and familial cases and the pattern of inheritance; 4) the genetic bases of essential tremor and Alzheimer?s disease; 5) effects of lead on cognitive performance and development of children; 6) relationships between occupational exposure to mercury vapor and the risk of tremor, peripheral neuropathy, cerebellar dysfunction and measures of abnormal balance; 7) mercury exposure derived from amalgams in the mouth and possible associations with neurological dysfunction or neuropsychological deficits; 8) caloric intake, body mass index and the risk of neurodegenerative disease; 9) mitochondrial function in normal aging, Parkinson s and Alzheimer s disease; 10) occupational mercury exposure and the risk of memory and visuospatial ability and disturbed mood; 11) molecular mechanisms of lead neurotoxicity; 12) mechanisms of manganese-induced Parkinsonism; and 13) molecular mechanisms of MPTP. Task-oriented working groups will be composed of selected members of the research core, facilities cores and Center staff as needed. The framework in which these work groups will operate will be flexible and will address specific research concentrations dictated by the overall focus of the Center. The specific aims are as follows: 1) to stimulate and guide interdisciplnary research on neurodegenerative diseases; 2) to stimulate and guide research on neurotoxicology with an emphasis on the neurotoxicity of transition and heavy metals; 3) to expand mechanistic and epidemiologic studies among the elderly of Northern Manhattan and; 4) to extend research efforts concerning the interaction of genetic susceptibility markers and environmental exposures in Parkinson?s and Alzheimer?s Disease. It is anticipated that highlights of meetings held in the 12 research areas will be presented at the bi-weekly work-in-progress meetings and that these meetings will provide a vehicle for communication of progress to other members of the Center and outreach programs.